Current topics in microbiology and immunology最新文献

Infectious mononucleosis is a clinical entity characterized by a sore throat, cervical lymph node enlargement, fatigue, and fever most often seen in adolescents and young adults. Infectious mononucleosis is most often caused by a primary Epstein-Barr virus (EBV) infection. EBV is a γ-herpesvirus that infects at least 90% of the population worldwide. The virus is spread by intimate oral contact among teenagers and young adults. How preadolescents acquire the virus is not known. A typical clinical presentation with a positive heterophile antibody test is usually sufficient to make the diagnosis, but heterophile antibodies are not specific and do not develop in some patients, especially preadolescent children. EBV-specific antibody profiles are the best choice for confirming and staging EBV infection. Besides causing acute illness during primary infection, there can also be long-term consequences from acquiring this virus, such as certain cancers and autoimmune diseases, as well as complications of primary immunodeficiency in persons with certain genetic mutations. Future challenges are to develop prophylactic and therapeutic vaccines and effective specific treatment strategies.

The rising prevalence of antibiotic resistance is rendering certain antibiotics ineffective in treating bacterial infections of public health importance. Deepening our understanding of how these drugs induce bacterial cell death, and whether antibiotics trigger a cell death program compared to direct killing, could help generate novel antibiotics or modify existing therapeutic approaches to improve clinical outcomes. Among the most widely used bactericidal antibiotics (beta-lactams, aminoglycosides, and fluoroquinolones), the primary drug-target interactions, and how they induce cell death, are well characterized. Additionally, there has been a recent debate as to whether a generalized bacterial cell death mechanism exists, shared among bactericidal antibiotics. The hypothesized mechanism, referred to as the common reactive oxygen species (ROS) pathway in this chapter, argues that certain bactericidal antibiotics have off-target effects that increase ROS generation in an iron- and oxygen-dependent manner. Moreover, this spike in ROS is thought to also contribute to induced bacterial cell death. Here we will discuss the target-specific mechanisms of distinct classes of bactericidal antibiotics, how these promote bacterial cell death, and the data that both support and refute the existence of a common cell death pathway.

Nearly two decades after the discovery of Epstein-Barr virus (EBV), the latent membrane protein 1 (LMP1) was identified and recognized as the primary transforming gene product of the virus. LMP1 is expressed in most EBV-associated lymphoproliferative diseases and malignancies, where it plays a central role in pathogenesis. Over 40 years of research have established LMP1 as a potent driver of cellular transformation and survival, deregulating key signaling pathways, cellular metabolism, and transcription while simultaneously subverting programmed cell death mechanisms. Beyond its role in transformation and immortalization, LMP1 exerts multifaceted biological activities supporting tumorigenesis, including immune modulation, regulation of the tumor microenvironment, and promotion of migration and invasive tumor growth. Functioning as a constitutively active receptor that mimics co-stimulatory CD40 receptor signals in B-lymphocytes, LMP1 recruits cellular signaling molecules associated with tumor necrosis factor receptors (TNFRs), such as TNFR-associated factors (TRAFs) and the TNFR-associated death domain protein (TRADD). It triggers phosphorylation, ubiquitination, and SUMOylation events in the target cell to activate NF-κB, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), interferon regulatory factor (IRF), and STAT pathways. This review provides an updated and comprehensive overview of the biological and molecular functions of LMP1, highlighting its role as a critical interface in virus-host interactions and its potential as a therapeutic target.

Epstein-Barr virus (EBV) infects more than 90% of adults worldwide. Following the initial infection, the host immune system launches an antiviral response involving both innate and adaptive immune functions. EBV establishes a persistent, lifelong infection, and to achieve this, it must carefully regulate the host immune response. By striking a balance between viral replication and immune defense, the pathogenic effects of EBV are minimized while its presence is maintained. This chapter explores some of the immune-modulating strategies employed by EBV, particularly its interference with various arms of innate and adaptive immunity, including the MHC-I and MHC-II antigen presentation pathways.

Epstein-Barr Virus (EBV) establishes latent infection as a circular, chromatinized episome that can persist in the nucleus of dividing and quiescent B cells, as well as in some NK, T, and epithelial cancer cells. During latency, the viral genome can express a diverse program of viral genes that have profound effects on the host cell, including capacity for immortalization, metabolic shifts, and immune evasion. The selective expression of viral genes during latency requires complex coordination between viral and host factors. This coordination is regulated by the chromatin structure and epigenetic programming of the viral genome. Epigenetic programming is determined by chromatin assembly, nucleosome positioning, histone and DNA modifications, transcription factor binding, RNA polymerase signaling, DNA looping, higher-ordered chromatin architecture, and interactions with host chromosome domains and territories. In addition, the latent viral genome divides using host replication and chromosome segregation machinery. Under stress conditions, the viral episome can switch into a lytic cycle where many additional viral factors are expressed to control late gene expression and viral rolling-circle replication followed by virion assembly and packaging. How the chromatin structure of the virus controls and is coordinated with all of these different processes and transitions is the focus of this chapter. Here we highlight recent advances in EBV chromatin control since the first edition of this chapter.

Epstein-Barr virus (EBV) homologues from non-human primates (NHPs) have been studied for nearly as long as EBV itself. Early serologic and DNA hybridization studies uncovered the existence of EBV-like lymphocryptoviruses (LCVs) across multiple NHP species. Subsequent molecular and genomic analyses revealed that LCVs from both humans and NHPs share strikingly similar colinear genome organization and encode homologous proteins expressed during both latent and lytic phases of infection, despite a level of species-specific restriction being present as shown by cross-infection experiments. Importantly, rhLCV infection in rhesus macaques faithfully recapitulates key aspects of EBV infection in humans, allowing for a powerful EBV surrogate animal model to study EBV infection and pathogenesis. In parallel, EBV susceptibility in the common marmoset offers a more accessible platform for EBV vaccine development with the potential to complement rhLCV studies. This chapter builds upon the First Edition of this work by taking the original text, beautifully crafted by Drs. Janine Mühe and Fred Wang, and updating it with relevant new insights and information. The updated chapter reviews over six decades of progress in characterizing LCVs that naturally infect primates, highlights the transformative use of rhesus macaques and common marmosets as experimental models of EBV infection, and explores how these systems are shaping the future of EBV research and vaccine development.

Although the role of Epstein-Barr virus (EBV) in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been obtained compellingly for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE). In contrast, evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify these conclusions and their implications for prevention and treatment.

Climate plays a crucial role in shaping dengue virus (DENV) transmission dynamics by influencing directly the physical and behavioural traits of mosquito individuals and viral replication. This chapter describes and evidences the intricate relationships between climate variables, mosquito traits and DENV transmission, highlighting the importance of understanding such connections in the context of a growing DENV burden and a global environmental change.

Epstein-Barr virus (EBV) infection has been associated with an expanding range of acute inflammatory, malignant, and autoimmune disorders. Seroepidemiological studies, facilitated by the early identification of key immunodominant targets of the EBV-specific humoral response, have provided invaluable insights into pathogenicity and global prevalence and incidence of EBV infections. These studies have also identified distinct antibody signatures associated with both the acute and persistent phases of infection, as well as EBV-related disorders. Over time, research into the humoral immune response against EBV has progressed from traditional cell-based immunofluorescence methods to high-throughput multiplex assays utilizing recombinant proteins or synthetic peptides as substrates. These improvements have shifted the focus from individual immunodominant antigens to the entire EBV proteome, enhancing our understanding of antiviral antibody responses in both health and disease. Detailed analyses of antigenic epitopes have uncovered significant biochemical and sequence homology between viral and host proteins, providing a conceptual framework for understanding the development of autoimmune diseases by a phenomenon known as antigenic mimicry. Recently, research has shifted toward translating these immune response findings into therapeutic strategies aimed at inducing or restoring immunity in patients with EBV-associated disorders. This chapter seeks to provide a comprehensive overview of the humoral immune response to EBV in healthy virus carriers and patients with EBV-associated disorders, tracing developments from the discovery of the virus 60 years ago to the present day and offering a perspective on future directions.